3-derivatives of the saturated and unsaturated androstane-3-one-17-ols substituted in 17-position and process of making same as well as the corresponding free ketones



Patented Oct. 9, 1945 3-DERIVATIVES OF THE SATURATED AND UNSATURATED ANDROSTANE-3-ONE-17- OLS SUBSTITUTED IN 17-POSITION AND PROCESS OF MAKING SAME AS WELL AS THE CORRESPONDING FREE KETONES Karl Miescher, Riehen, Switzerland, assignor to Ciba Pharmaceutical Products Incorporated. Summit, N. J., a corporation No Drawing. Application November 10, 1943, Se-

rial No. 509,776. In Switzerland December 10,

8 Claims. (Cl. 260239.5)

This application is a continuation in part of my copending application Serial No. 306,184, filed November 25, 1939.

It is known that saturated and unsaturated androstanolones containinga substituent, for ex- 5 Instead of the androstendione-3-mono-enol.. ample a saturated or unsaturated hydrocarbon ethylether one may start also from other androradical, in the l'l-position and a keto group in stendione-3-mono-enol-ethers, for example the the 3-position, may be obtained by treating cormethyl-, propyl-, benzylor trityl-ethers or even responding 3-oxy-compounds with oxidizing from corresponding 3-mono-enolesters or -aceagents. Such a final oxidation, however, has tals. shown itself in many cases to be undesirable. It The 1'l-methyl-dihydro-testosterone for exhas .now been found that it may be avoided if ample, may be obtained in a similar manner for metallo-organic compounds are allowed to react example from the 3-g1ycol-aceta1, other 3-monoon 3-enolates or 3-acetals of saturated or unacetals, 3-mono-enolethers or -esters of androsaturated androstandiones, and, if required, the standione. derivatives thus obtained are hydrolyzed. e 0011018 epimeric in 7-p0sition may a so As parent substances, for example the 3-en0l be separated from the mother liquors of the reethers, like 3-methylor 3-ethyl-enol ethers as c on product. well as the 3-enol esters and the 3-acetals, for 1 Example 2 example the 3-glycolates or 3 -propandiolates, of 2c 35 gms of androstendi0ne 3 mono ethylene androstendiones or androstandiones or their deglycoha'ce'tal Pt. 2000, obtainable by condem rivatiives may be used- These a p prepared t sation of androstendione with ethyleneglycol in cording to the data of the publication of A Sermi presence of acid as catalyst) gms of magne and A. Kloster in Berichte der deutschen chem- 5mm some activated maghesmm opper auoy ischen Gesellschaft, vol. :71, page 1766 (1938). 25 and of ether are Stirred in a flask Into Suitable metallo-qrgamc compounds for this, '70 cc, of allyl-bromide are dropped, when example the magnesmm Organ) compounds F gentle reaction takes place. After the reaction alkyl (like methyl, ethyl), alkylene- (1}ke has started, boiling is continued for 2 hours if aralkyl" ,(nke b enzyl) Y (hke necessary by externally warming the flask with phenyl-) magnesium halides, further zinc-alkyl 0 warm water. The reaction mixtureis then cooled Wounds and the1ikewith ice and treated with 200 cc. of water. Di-

As products of the present invention there may luted sulfuric acid is added till acid to congo be named for example the 3-derlvatlves llke and the whole shaken at 0 to split the 17- enolates (3-eno1-ethers or esters) or B-acetals of 1 t t ne-3 ethyleneglycol-acetal conthe saturated an unsaturated androstane-B-one- 35 tamed in the ether The ethertqayer is then 174315 containing in 17-130mm saturated hydro arated, dried and evaporated. From the residue carbon radicals like alkyl groups (methyl, ethyl there is Obtained by chromatography the known roups) or hydrocarbon radicals containing 17-allyl-testosterone. In a similar manner other double bondsl allylbenzyl-groups- 3-acetals of saturated or unsaturated androstanethefmore then hydrolysation products contam" 0 3-one-17-ols containing in l'l-position a satumg free 3'keto'groups are 94150 obtamedrated or unsaturated hydrocarbon radical, e. 3. Example 1 17-methy1-testosterone-3-acetals or 1'7-methy1..

' dihydrotestosterone-3-acetals, and their hydro- [A solution of 63 gm. of androstendione-B- lysation products are obtained. monoenol-ethylether in toluene is allowed to WhatIclaim is: drop into an ethereal solution of 72 gms, of 1. Process for the manufacture of amember of methyl-magnesium bromide. The mixed solutions the group consisting of the saturated and unsatuare then boiled for some time. After the reacrated androstanolones substituted in 17-position tion is complete, the solution is decomposed with and derivatives thereof, comprising allowing an excess of ammonium chloride solution and the 0 allyl-magnesium halide to react on a member of layers are separated. The 3-enol ether of the the group consisting of the 3-acetals of saturated l'l-methyl-testosterone is obtained after concen-. and unsaturated androstandiones, an then hytration of the organic solution and may easily be drolyzing the derivatives obtained. converted by an acid agent into the known 17- 2. The 3-acetals of the saturated and unsatumethyl-testosterone. In an analogous manner 56 rated androstane-3-one-17-ols containing in 17- also the 17-ethyl-, -allyl-, or -benzyl-testosterones are obtained. The corresponding Grignard-reagents may be replaced for example by zinc derivatives.

5. The 3-aceta1s of the saturated and unsaturated androstane-ii-one-l'I-ols containing in 17- position an allyl group.

6. The 17-methy1-testosterone-Ii-acetals.

7. The tals.

1'7-methyl-dihydrotestosterone-3-ace- 8. 17-a1lyl-testosterone-3-ethyleneg1ycol ace- KARL MIESCHER. 

